Biological Rationale for prevention of COVID-19 disease with BCG vaccine

The primary treatment for COVID-19 that caused shutdown in world economy and resulted in millions of deaths is still supportive and specific antiviral therapy is yet to be developed. The rapid growth of the COVID-19 pandemic worldwide therefore encouraged global efforts to urgently design and test several vaccine candidates within a very short period of time. Although several vaccines have been developed but still there is significant shortage which is expected to be in years before it can reach majority of the world specially in low-income countries. Therefore, there is a need to develop other measures to prevent the spread of the virus. Numerous studies have shown previously that the Bacillus Calmette−Guerin (BCG) vaccine causes a reduction in infant mortality. This protection could not be explained by a reduction in tuberculosis alone. Indeed, It was found that the BCG vaccine provided protection against infectious diseases not related to Tuberculosis, specifically neonatal sepsis and respiratory tract infections. Furthermore, BCG was also found to have protective effects against inflammatory diseases. It is thought that these protective effects of the BCG vaccine were caused by a long-term general boosting of the innate immune mechanism, which implied the presence of metabolic and epigenetic reprogramming of innate immune cells. Some recent studies have demonstrated that there is a strong association between COVID-19 incidence and total deaths and the presence or absence of national mandatory BCG vaccination programs. This has resulted in recommendations for the initiation of further studies that will support revaccination with BCG as a way to reduce COVID-19 incidence and severity.

To study further the BCG vaccine and COVID-19, University of Belgrade scientists: Dr. Sanja Dr. Glisic, Dr. Vladimir Perovic and Dr. Milan Sencanski together with Dr. Slobodan Paessler at University of Texas and Dr. Veljko Veljkovic at Biomed Protection explored the relationship between the BCG vaccine and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, responsible for COVID-19.  Their findings showed that some strains in the BCG vaccine had the potential to induce an immune response against SARS-CoV-2. The original research article is published in the Journal of Proteome Research.

The research team observed that in countries with a compulsory BCG vaccination implemented, the number of COVID-19 cases and associated deaths and mortality rates were significantly lower compared to countries with no or interrupted BCG vaccination. They also found a physical property essential for the interaction between S proteins of SARS-CoV and SARS-CoV-2 and their receptor ACE2. This same physical property was found in three out of six principal antigens of the BCG vaccine which correspond to Mycobacterium tuberculosis proteins.

Furthermore, in order to identify any other BCG antigens that could induce an immune response against SARS-CoV-2, the authors conducted an analysis for immunological properties. They found that only one out of nine selected BCG proteins represented an antigen that is recognized by Tuberculosis patients’ immune system.

In summary, the authors have been able to demonstrate that some bacterial proteins from the BCG vaccine share similar key properties with the S1 protein of SARS-CoV-2. This may explain the possibility of an immunological cross-reaction between the S1 protein and these bacterial proteins, which could result in a specific adaptive immune response against SARS-CoV-2. The authors believe that if the conclusion from this study is confirmed experimentally, then it could serve as the basis for the development of rapid BCG vaccine with improved protection against COVID-19 which can be deployed specially in low-income countries and by this slow the COVID-19 pandemic worldwide and reduce unnecessary loss of life.